Mechanisms by which missense variants in myosin and myosin-binding protein C alter cellular contractility in genetic cardiomyopathies


  • Dr Christopher Toepfer

    University of Oxford

Project summary

Heart disease is a leading cause of death in the UK and around the world and its prevalence continues to grow. Heart failure occurs when cardiac muscle is unable to meet the body’s demands for oxygen and nutrients. It can emerge due to many factors which alter the heart’s structure and function.

I aim to discover the molecules and pathways that are changed by genetic factors that cause heart failure. I will introduce specific genetic changes identified in human volunteers into human stem cells that can become beating heart cells. Using this ‘heart-on-a-dish’ system, I will compare the contraction and relaxation, biochemistry, and molecular responses of cultured heart cells and tissues to discover the important processes that allow heart muscle to function or to fail. I want to understand how genetic changes in the same gene cause different forms of heart failure and whether two closely related genes cause a similar type of heart failure and which genetic changes lead to heart failure and which do not.

This research will discover mechanisms of disease that can inform new therapies to limit or prevent human heart failure.